Specialized dendritic cells in cross-presentation of exogenous antigens to cytotoxic T lymphocytes

Abstract

Dendritic cells (DC) are cells of hematopoietic origin, which constitutively express MHC class I and II, and are functionally the most potent inducers of T-lymphocyte activation and proliferation. CD8+ T lymphocytes proliferate and acquire cytotoxic functions upon recognition of their cognate antigen on the surface of one or various dendritic cells contacts. However, only some DC subsets are able to present antigen to cytotoxic T cell precursors as taken up from extracellular sources. This function is termed crosspresentation (in Spanish, presentación cruzada o presentación subrogada) and requires shuttle mechanisms from phagosomes to the cytosol for antigen processing. It has been demonstrated that the differentiation of DC with these capabilities is dependent on FLT-3L and the transcription factor BATF3. They express peculiar functions and differentiation markers. Surface CD8a features these cells in mice while CD141 (BDCA-3) marks these cells in the human. These subpopulations are capable of selective internalization of necrotic cell debris by means of their CLEC9A lectin that is a receptor for extracellular polymerized actin. Expression of the chemokine receptor XCR1 favours contact with CD8+ T cells. Therapeutic vaccination with tumor antigens using DC is a strategy under development for the treatment of cancer. The use of DC subsets with more prominent capabilities for crosspresentation would mimic the natural mechanisms of immunization to induce cytolitic T lymphocytes. In vivo targeting of antigen with monoclonal antibodies against DEC-205 or CLEC9A attains very robust immune responses and is a strategy undergoing clinical trials for chronic viral diseases and malignancies.